POS0714 POOLED SAFETY ANALYSIS OF BARICITINIB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM THREE RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CLINICAL TRIALS
Authors: T. Dörner, Y. Tanaka, M. Mosca, I. N. Bruce, M. Cardiel, E. F. Morand, M. A. Petri, M. Silk, C. Dickson, G. Meszaros, M. Issa, L. Zhang, D. J. Wallace
Journal: Annals of the Rheumatic Diseases (2022)

Background Baricitinib (BARI), an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis and atopic dermatitis, has been evaluated in clinical studies in patients with systemic lupus erythematosus (SLE). Objectives To assess the safety profile of BARI in patients with SLE. Methods Patients with SLE receiving stable background therapy were randomised 1:1:1 to BARI 2-mg, 4-mg, or placebo (PBO) once daily in one 24-week, phase 2 ( NCT02708095 ) and two 52-week, phase 3, PBO controlled studies ( NCT03616912 and NCT03616964 ). Results A total of 1,849 patients were included in this pooled analysis, representing 1,463.5 patient years of exposure (PYE). The incidence rates per 100 PYR at risk (IR/100 PYR) for serious adverse events (SAEs) were 9.5, 14.7, and 14.1 respectively for PBO, BARI 2-mg, and BARI 4-mg. There were no clinically meaningful differences between treatment groups for discontinuations due to AEs or death (Table 1). Table 1. Overview of safety measures of baricitinib in patients with SLE Safety measure PBO BARI 2-mg BARI 4-mg Pooled-BARI N=614 N=621 N=614 N=1235 PYE=488.1 PYE=494.0 PYE=481.4 PYE=975.4 n(%) n(%) n(%) n(%) PYR PYR PYR PYR [IR; 95%CI] [IR; 95%CI] [IR; 95%CI] [IR; 95%CI] SAEs 45 (7.3) 70 (11.3)* 65 (10.6)* 135 (10.9)* 473.2 476.6 461.9 938.5 [9.5; 6.9, 12.7] [14.7; 11.5, 18.6] [14.1; 10.9, 17.9] [14.4; 12.1, 17.0] Discontinuation of study drug due to AE 48 (7.8) 58 (9.3) 57 (9.3) 115 (9.3) 485.3 492.3 480.6 973.0 [9.9; 7.3, 13.1] [11.8; 8.9, 15.2] [11.9; 9.0, 15.4] [11.8; 9.8, 14.2] Death 4 (0.7) 1 (0.2) 4 (0.7) 5 (0.4) 488.2 494.0 481.5 975.5 [0.8; 0.2, 2.1] [0.2; 0.0, 1.1] [0.8; 0.2, 2.1] [0.5; 0.2, 1.2] Serious infections 12 (2.0) 22 (3.5) 28 (4.6)* 50 (4.0)* 484.3 487.2 472.5 959.7 [2.5; 1.3, 4.3] [4.5; 2.8, 6.8] [5.9; 3.9, 8.6] [5.2; 3.9, 6.9] Herpes Zoster 18 (2.9) 17 (2.7) 29 (4.7) 46 (3.7) 481.1 486.5 468.6 955.1 [3.7; 2.2, 5.9] [3.5; 2.0, 5.6] [6.2; 4.1, 8.9] [4.8; 3.5, 6.4] VTEs# 6 (1.2) 3 (0.6) 1 (0.2) 4 (0.4) 444.0 450.2 438.1 888.3 [1.4; 0.5, 2.9] [0.7; 0.1, 1.9] [0.2; 0.0, 1.3] [0.5; 0.1, 1.2] MACE# 0 1 (0.2) 3 (0.6) 4 (0.4) 443.9 450.1 438.1 888.3 [0.0; NA, 0.8] [0.2; 0.0, 1.2] [0.7; 0.1, 2.0] [0.5; 0.1, 1.2] Malignancy excluding NMSC 2 (0.3) 3 (0.5) 2 (0.3) 5 (0.4) 488.0 494.1 481.4 975.5 [0.4; 0.0, 1.5] [0.6; 0.1, 1.8] [0.4; 0.1, 1.5] [0.5; 0.2, 1.2] NMSC 2 (0.3) 0 0 0* 486.7 494.0 481.4 975.4 [0.4; 0.0, 1.5] [0.0; NA, 0.7] [0.0; NA, 0.8] [0.0; NA, 0.4] Data are n (%) patients PYR [IR; 95% CI]. #Phase 2 study data not included. AE=adverse event; CI=confidence interval; MACE=major adverse cardiac event; NMSC=non-melanoma skin cancers; VTE=venous thrombotic event (includes deep vein thrombosis and pulmonary embolism); IR=incidence rate (100 times the number of patients reporting an adverse event divided by the event-specific exposure to treatment); N=number of patients in the analysis population; n=number of patients in the specified category; PYE=patient-year of exposure; PYR=patient years at risk; SAE=serious adverse event. *p≤0.05 vs placebo. The IR/100 PYR for serious infections were 2.5, 4.5, and 5.9 respectively for PBO, BARI 2-mg, and BARI 4-mg. The risk of Herpes Zoster was higher in BARI 4-mg (4.7%) vs PBO (2.9%) (Table 1). The IR/100 PYR for positively adjudicated venous thrombotic events (VTEs) were 1.4, 0.7, and 0.2 respectively for PBO, BARI 2-mg, and BARI 4-mg. The IR/100 PYR for positively adjudicated major adverse cardiac event (MACE) was numerically higher in BARI 2-mg (0.2) and BARI 4-mg (0.7) vs PBO (0.0), however the pooled-BARI IR/PYR (0.5) was within the range of background disease (1). No increased risk for malignancies was observed. Conclusion The safety profile of BARI in SLE patients was consistent with the known BARI safety profile. There was no increased risk of VTE in BARI treatment groups. References [1]Barbhaiya M, Feldman CH, et al. Arthritis Rheumatol. 2017;69(9):1823-31. Disclosure of Interests Thomas Dörner Speakers bureau: Eli Lilly and Company and Roche, Consultant of: AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, Roche, Samsung and UCB, Grant/research support from: Chugai, Janssen, Novartis and Sanofi, Yoshiya Tanaka Speakers bureau: Gilead, Abbvie, Behringer-Ingelheim, Eli Lilly, Mitsubishi-Tanabe, Chugai, Amgen, YL Biologics, Eisai, Astellas, Bristol-Myers, Astra-Zeneca, Consultant of: Eli Lilly, Daiichi-Sankyo, Taisho, Ayumi, Sanofi, GSK, Abbvie, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Mitsubishi-Tanabe, Eisai, Takeda, Corrona, Daiichi-Sankyo, Kowa, Behringer-Ingelheim, Marta Mosca Speakers bureau: Eli Lilly, GSK, Astra Zeneca, Consultant of: Eli Lilly, GSK, Astra Zeneca, Ian N. Bruce Speakers bureau: GSK, Astra Zeneca, UCB, Consultant of: Eli Lilly, GSK, UCB, BMS, Merck Serono, Astra Zeneca, IL-TOO, Aurinia, Grant/research support from: GSK, Janssen, Mario Cardiel Speakers bureau: Eli Lilly, Pfizer, Abbvie, Consultant of: Eli Lilly, Pfizer, Grant/research support from: Pfizer, Gilead, Roche, Janssen, Eric F. Morand Speakers bureau: AstraZeneca, Eli Lilly, Novartis, Consultant of: Amgen, AstraZeneca, Asahi Kasei, Biogen, BristolMyersSquibb, Capella, Eli Lilly, EMD Serono, Genentech, GlaxoSmithKline, Janssen, Neovacs, Sanofi, Servier, UCB, Wolf, Grant/research support from: Janssen, AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, GlaxoSmithKline, Michelle A Petri Consultant of: Eli Lilly, Grant/research support from: Eli Lilly, Maria Silk Shareholder of: Eli Lilly, Employee of: Eli Lilly, christina dickson Shareholder of: Eli Lilly, Employee of: Eli Lilly, Gabriella Meszaros Shareholder of: Eli Lilly, Employee of: Eli Lilly, Maher Issa Shareholder of: Eli Lilly, Employee of: Eli Lilly, Lu Zhang Shareholder of: Eli Lilly, Employee of: Eli Lilly, Daniel J. Wallace Consultant of: Amgen, Eli Lilly and Company, EMD Merck Serono and Pfizer